肾小球特异性 Lin28A 过表达引发严重炎症反应和肾损伤

IF 8.2 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY International Journal of Biological Sciences Pub Date : 2024-07-22 eCollection Date: 2024-01-01 DOI:10.7150/ijbs.97434
Anna Futorian, Leah Armon, Hiba Waldman Ben-Asher, Irit Shoval, Inbal Hazut, Ariel Munitz, Achia Urbach
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引用次数: 0

摘要

RNA 结合蛋白 LIN28A 和 LIN28B 有助于多种发育生物过程。Lin28A和Lin28B的表达失调与多种肿瘤有关。本研究表明,Lin28A 在小鼠肾小球中的过表达会导致严重的炎症和肾损伤,而不是肿瘤发生。值得注意的是,Lin28A的过表达仅在肾小球中表达时才会导致炎症,而在肾脏的基质细胞中表达时不会,这突出了它的细胞环境依赖性。肾小球特异性 Lin28A 诱导的炎症反应不同于之前描述的 Lin28B 介导的炎症反馈回路,因为它独立于 IL-6。相反,它与 Cxcl1 和 Ccl2 等细胞因子的快速上调有关。这些发现表明,Lin28A 过表达的病理生理效应超出了细胞转化的范围。我们的转基因小鼠模型为我们进一步了解急性肾损伤的病理生理学提供了一个宝贵的工具,而炎症是急性肾损伤的一个关键因素。
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Nephron-Specific Lin28A Overexpression Triggers Severe Inflammatory Response and Kidney Damage.

The RNA-binding proteins LIN28A and LIN28B contribute to a variety of developmental biological processes. Dysregulation of Lin28A and Lin28B expression is associated with numerous types of tumors. This study demonstrates that Lin28A overexpression in the mouse nephrons leads to severe inflammation and kidney damage rather than to tumorigenesis. Notably, Lin28A overexpression causes inflammation only when expressed in nephrons, but not in the stromal cells of the kidneys, highlighting its cell context-dependent nature. The nephron-specific Lin28A-induced inflammatory response differs from previously described Lin28B-mediated inflammatory feedback loops as it is IL-6 independent. Instead, it is associated with the rapid upregulation of cytokines like Cxcl1 and Ccl2. These findings suggest that the pathophysiological effects of Lin28A overexpression extend beyond cell transformation. Our transgenic mouse model offers a valuable tool for advancing our understanding of the pathophysiology of acute kidney injury, where inflammation is a key factor.

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来源期刊
International Journal of Biological Sciences
International Journal of Biological Sciences 生物-生化与分子生物学
CiteScore
16.90
自引率
1.10%
发文量
413
审稿时长
1 months
期刊介绍: The International Journal of Biological Sciences is a peer-reviewed, open-access scientific journal published by Ivyspring International Publisher. It dedicates itself to publishing original articles, reviews, and short research communications across all domains of biological sciences.
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